A number of diagnostic tests are routinely performed on humans to evaluate the amount or existence of substances present in blood or other body fluids. These diagnostic tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin. One particular diagnostic test entails self-monitoring of blood glucose levels by people with diabetes.
Diabetes is a major health concern, and treatment of the more severe form of the condition, Type 1 (insulin-dependent) diabetes, requires one or more insulin injections per day. Insulin controls utilization of glucose or sugar in the blood and prevents hyperglycemia which, if left uncorrected, can lead to ketosis. On the other hand, improper administration of insulin therapy can result in hypoglycemic episodes, which can cause coma and death. Hyperglycemia in diabetics has been correlated with several long-term effects of diabetes, such as heart disease, atherosclerosis, blindness, stroke, hypertension and kidney failure.
The value of frequent monitoring of blood glucose to avoid or at least minimize the complications of Type 1 diabetes is well established. Patients with Type 2 (non-insulin-dependent) diabetes can also benefit from blood glucose monitoring in the control of their condition by way of diet and exercise.
Conventional blood glucose monitoring methods generally require the drawing of a blood sample (e.g., by fingerprick) for each test, and a determination of the glucose level using an instrument that reads glucose concentrations by electrochemical or colorimetric methods. Type 1 diabetics must obtain several fingerprick blood glucose measurements each day in order to maintain tight glycemic control. However, the pain and inconvenience associated with this blood sampling, along with the fear of hypoglycemia, has led to poor patient compliance, despite strong evidence that tight control dramatically reduces long-term diabetic complications. In fact, these considerations can often lead to an abatement of the monitoring process by the diabetic. See, e.g., The Diabetes Control and Complications Trial Research Group (1993) New Engl. J. Med. 329:977–1036.
Recently, various methods for determining the concentration of blood analytes without drawing blood have been developed. Some of these methods use hydrogels. A number of hydrophilic, polymeric compounds are known to form a gel in the presence of water, for example, 2% gelatin in water, obtained by the hydrolysis of collagen by boiling skin, ligaments, tendons, etc., will form a gel. A hydrogel may be formed by adding a solute, such as gelatin, to water at an elevated temperature to dissolve gelatin. The solution is then cooled and the solute(s) (e.g., solid gelatin components) forms submicroscopic crystalline particle groups which retain a great deal of solvent (generally water) in the interstices.
Gels may be formed from naturally occurring or synthetic materials and have a wide range of uses including photographic film, sizing, textile and paper adhesives, capsules and patches for medicinals, and patches used with electronic medical monitoring equipment. U.S. Pat. No. 5,405,366 to Fox et al. describes the formation of a non-stringy adhesive hydrophilic gel for use in delivering medicaments to a patent. The gels are formed, for example, by crosslinking the water soluble N-vinyl-2-pyrrolidone polymer under conditions such that the gel is free of unbound water. U.S. Pat. No. 5,143,071 to Keusch et al. also describes the formation of non-stringy adhesive gels by crosslinking poly(vinyl pyrrolidone) or poly(ethylene oxide).
Gel formulations for use in analyte monitoring devices have been described in PCT International Publication Nos. WO 97/02811 and WO 00/64533.
The present invention provides gel compositions, as well as compositions of ionically conductive materials, and methods that provide enhanced transdermal flux of analyte and improved performance of analyte monitoring systems.